Key Factors Influencing IO Continuation or Discontinuation in Subsequent Lines of Treatment in Advanced EC

Summary for Physicians: Factors Influencing the Decision to Continue or Discontinue IO in Subsequent Lines for Advanced EC

The decision to continue or discontinue IO therapy in subsequent lines of treatment for advanced EC is influenced by a variety of factors:

• Tumor Response to Initial Therapy:
  • Initial response to IO therapy is one of the primary factors in determining whether to continue or discontinue. Patients who show a partial or complete response are more likely to benefit from continuing IO therapy in subsequent lines.
  • Conversely, patients with progressive disease despite initial IO treatment may need to switch to other therapeutic options.
    
• Biomarker Status:
  • Mismatch repair status (dMMR), microsatellite instability (MSI), and tumor mutational burden play a critical role in the decision. Patients with dMMR or MSI-high tumors tend to respond better to IO therapies, and if they have shown initial benefit, continuing IO may be considered.
  • Biomarker reassessment at progression is often needed to guide whether IO can still be effective or whether a switch to another therapy is warranted.
    
• Tolerability and Adverse Effects:
  • The toxicity profile and tolerability of IO therapy are crucial considerations. If a patient is experiencing significant adverse effects, it may influence the decision to discontinue or adjust the dose of IO therapy.
  • Balancing the risk-to-benefit ratio is key, especially if the patient’s quality of life is impacted by treatment-related adverse effects.
    
• Patient Performance Status and Comorbidities:
  • The patient's performance status and presence of comorbidities can influence the decision to continue IO. Patients with a high performance status and minimal comorbid conditions may benefit from continuing IO therapy, while those with poor performance status or significant comorbidities may require treatment modifications.
    
• Previous Treatment History:
  • The patient’s prior treatment history and the sequence of therapies already administered (eg, IO with chemotherapy, prior lines of chemotherapy, or other targeted therapies) will influence the decision to continue or discontinue IO. If IO has been used earlier in the treatment course, it may be less likely to be effective in subsequent lines.
    
• Availability of Alternative Therapies:
  • If there are effective alternative therapies available, such as targeted therapies (eg, lenvatinib, mTOR inhibitors), chemotherapy, or clinical trial options, these may be considered instead of continuing IO.
    
• Clinical Trial Participation:
  • Participation in clinical trials for new IO therapies or combination treatments may be an option, especially for patients who have progressed on prior IO therapy.

In summary, the decision to continue or discontinue IO therapy in subsequent lines of treatment is a dynamic process that considers tumor response, biomarker status, treatment tolerability, patient health, and the availability of alternative therapies. Each decision should be personalized to the individual patient based on these critical factors.